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Related Experiment Video

Updated: Jan 14, 2026

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Can maternal metformin protect the developing fetal brain?

Claudia Ibarra1, Baharan Fekry1, Lierni Ugartemendia1

  • 1Department of Obstetrics, Gynecology, & Reproductive Sciences, Division of Maternal-Fetal Medicine, UTHealth, Houston, TX.

American Journal of Obstetrics and Gynecology
|October 23, 2025
PubMed
Summary
This summary is machine-generated.

Maternal metformin treatment during pregnancy increased fetal brain Sirtuin-1 levels, a biomarker associated with neuroprotection and healthy brain development. This finding suggests potential benefits of metformin for fetal brain health in mothers with diabetes.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pharmacology

Background:

  • Maternal diabetes increases risks for autism spectrum disorder and attention-deficit hyperactivity disorder in offspring.
  • Metformin shows emerging neuroprotective potential in preclinical and clinical studies.
  • Fetal neuronally derived extracellular vesicles offer a non-invasive window into fetal neurodevelopment.

Purpose of the Study:

  • To investigate the effects of maternal metformin treatment on fetal brain health biomarkers.
  • To assess Sirtuin-1, tumor necrosis factor-alpha, and Bcl-2-associated X protein levels in fetal neuronally derived extracellular vesicles.

Main Methods:

  • A nested case-control study analyzed maternal serum from a metformin vs. insulin trial for diabetes in pregnancy.
  • Fetal neuronally derived extracellular vesicles were isolated and key protein biomarkers quantified.
  • Correlation between vesicle and fetal brain tissue biomarker concentrations was validated.

Main Results:

  • Maternal metformin use was associated with a significant increase (39%) in fetal brain Sirtuin-1 levels within extracellular vesicles.
  • No significant differences were found for other assessed biomarkers (tumor necrosis factor-alpha, Bcl-2-associated X protein).
  • Vesicle Sirtuin-1 levels strongly correlated with fetal brain tissue concentrations, validating their use as a proxy.

Conclusions:

  • Maternal metformin treatment positively impacts fetal brain development by increasing Sirtuin-1, supporting neuronal differentiation and preventing mitochondrial loss.
  • Sirtuin-1 plays a crucial role in cognitive function and brain plasticity.
  • Findings inform the risk-benefit analysis of metformin use in pregnant women with diabetes.